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1. 发明申请

US20120263625A1 GLYCO-SUBSTITUTED DIHYDROXY-CHLORINS AND ß-FUNCTIONALIZED CHLORINS FOR ANTI-MICROBIAL PHOTODYNAMIC THERAPY 有权
标题翻译：用于抗微生物光化学治疗的GLYCO取代的二羟基氯和ß-功能氯化物
公开(公告)号：US20120263625A1
公开(公告)日：2012-10-18
申请号：US13189113
申请日：2011-07-22
申请人： Daniel Aicher , Volker Albrecht , Burkhard Gitter , Christian B. W. Stark , Arno Wiehe
发明人： Daniel Aicher , Volker Albrecht , Burkhard Gitter , Christian B. W. Stark , Arno Wiehe
IPC分类号： C07H15/26 , A61L2/08
CPC分类号： A61K31/185 , A61K31/19 , A61K31/409 , A61K31/7056 , A61K41/0071 , A61K47/549 , C07H15/26
摘要： Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The key to these conjugates is connecting dihydroxychlorins or β-functionalized chlorins to carbohydrate moieties. These conjugates are found to be very effective in combating bacterial infections caused by Gram-positive and Gram-negative bacteria, including their resistant strains. Significantly, they are also effective in complex environments, including blood, serum, and other body fluids which are present in patient's body. A method of use to control pathogenic microorganisms in human and animals is also provided.
摘要翻译：提供了用于治疗和预防人和动物中致病微生物引起的感染性疾病的抗微生物分子缀合物。这些缀合物的关键是将二羟基二氢卟酚或二官能化的二氢卟酚连接到碳水化合物部分。发现这些缀合物对抗革兰氏阳性和革兰氏阴性细菌（包括其抗性菌株）引起的细菌感染是非常有效的。值得注意的是，它们在复杂的环境中也是有效的，包括血液，血清和患者体内存在的其他体液。还提供了用于控制人和动物中的病原微生物的方法。

2. 发明授权

US09308185B2 Glyco-substituted dihydroxy-chlorins and β-functionalized chlorins for anti-microbial photodynamic therapy 有权
标题翻译：糖基取代的二羟基二氢卟酚和用于抗微生物光动力治疗的功能性二氢卟酚
公开(公告)号：US09308185B2
公开(公告)日：2016-04-12
申请号：US13189113
申请日：2011-07-22
申请人： Daniel Aicher , Volker Albrecht , Burkhard Gitter , Christian B. W. Stark , Arno Wiehe
发明人： Daniel Aicher , Volker Albrecht , Burkhard Gitter , Christian B. W. Stark , Arno Wiehe
IPC分类号： C07H15/26 , A61K31/409 , A61K31/185 , A61K31/19 , A61K31/7056 , A61K41/00 , A61K47/48
CPC分类号： A61K31/185 , A61K31/19 , A61K31/409 , A61K31/7056 , A61K41/0071 , A61K47/549 , C07H15/26
摘要： Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The conjugates are of the class of compounds of dihydroxychlorins or β-functionalized chlorins connected to carbohydrate moieties and having the general formula
摘要翻译：提供了用于治疗和预防人和动物中致病微生物引起的感染性疾病的抗微生物分子缀合物。缀合物是与碳水化合物部分连接的二羟基二氢卟酚或二官能化二氢卟酚的化合物，具有通式

3. 发明授权

US08956648B2 Calciumphosphate-based nanoparticles as carrier-systems for photodynamic therapy 有权
标题翻译：基于磷酸钙的纳米粒子作为光动力疗法的载体系统
公开(公告)号：US08956648B2
公开(公告)日：2015-02-17
申请号：US13140855
申请日：2009-12-18
申请人： Burkhard Gitter , Susanna Gräfe , Arno Wiehe , Volker Albrecht , Matthias Epple , Janine Schwiertz , Kathirvel Ganesan
发明人： Burkhard Gitter , Susanna Gräfe , Arno Wiehe , Volker Albrecht , Matthias Epple , Janine Schwiertz , Kathirvel Ganesan
IPC分类号： A61P35/00 , A61P31/04 , A61K9/14 , A61K31/5415 , B82Y5/00 , A61K9/51 , A61K41/00 , A61K49/00
CPC分类号： A61K9/5115 , A61K41/0057 , A61K41/0071 , A61K49/0093 , Y10S977/773
摘要： The present invention provides pharmaceutical photosensitizer-loaded nanoparticle formulations and their methods of preparation for photodynamic therapy, comprising a hydrophobic or hydrophilic photosensitizer, nanoparticulate calcium phosphate and in certain cases auxiliary reagents such as stabilizers. The calcium phosphate-based nanoparticle formulations of the present invention provide excellent storage stability and therapeutically effective amounts of photosensitizer for intravenous or topical administration. In a preferred embodiment, tetrapyrrole derivatives such as porphyrins, chlorins and bacteriochlorins, are the preferred hydrophobic photosensitizers to be formulated in calcium phosphate nanoparticle formulations for photodynamic tumor therapy. Additionally, 5,10,15,20-tetrakis(4-phosphonooxyphenyl)porphine (pTPPP) is a preferred hydrophilic photosensitizer for photodynamic tumor therapy. In another preferred embodiment, hydrophilic cationic and anionic photosensitizers, especially those of the phenazinium, phenothiazinium and xanthenes series have been found to inactive pathogen bacteria and are the preferred photosensitizers to be formulated in calcium phosphate nanoparticle formulations for antibacterial photodynamic therapy. In another embodiment, photosensitizing nanoparticle formulations are useful to locate cells, tissues or bacteria by using fluorescence imaging methods.
摘要翻译：本发明提供负载药物的光敏剂纳米颗粒制剂及其制备光动力疗法的方法，其包括疏水或亲水性光敏剂，纳米颗粒磷酸钙，在某些情况下，辅助试剂如稳定剂。本发明的基于磷酸钙的纳米颗粒制剂提供优异的储存稳定性和用于静脉内或局部给药的治疗有效量的光敏剂。在优选的实施方案中，四吡咯衍生物如卟啉，二氢卟酚和细菌二氢卟酚是拟配制在用于光动力学肿瘤治疗的磷酸钙纳米颗粒制剂中的优选的疏水性光敏剂。另外，5,10,15,20-四（4-膦酰氧基苯基）卟吩（pTPPP）是用于光动力学肿瘤治疗的优选亲水性光敏剂。在另一个优选的实施方案中，已经发现亲水性阳离子和阴离子光敏剂，特别是吩嗪鎓，吩噻嗪和呫吨系列的亲水性阳离子和阴离子光敏剂是无活性的病原体细菌，并且是配制在用于抗菌光动力学治疗的磷酸钙纳米颗粒制剂中的优选的光敏剂。在另一个实施方案中，光敏纳米颗粒制剂可用于通过使用荧光成像方法定位细胞，组织或细菌。

4. 发明申请

US20050049228A1 Antimicrobial photodynamic therapy compound and method of use 审中-公开
标题翻译：抗微生物光动力治疗化合物及其使用方法
公开(公告)号：US20050049228A1
公开(公告)日：2005-03-03
申请号：US10860296
申请日：2004-06-03
申请人： Volker Albrecht , Burkhard Gitter
发明人： Volker Albrecht , Burkhard Gitter
IPC分类号： A61K41/00 , A61N5/06 , A61K31/655 , A61N1/30
CPC分类号： A61K41/0019 , A61K41/0057 , A61N5/062
摘要： A method and composition for destroying microbes, especially bacteria, in the body utilizing Safranin O in conjunction with electromagnetic radiation is disclosed. In a preferred method, a composition comprising Safranin O is introduced to a treatment area. After a sufficient period of time has elapsed, radiation of a suitable wavelength is applied to the area to activate the Safranin O and by a photodynamic reaction to destroy the bacteria. Preferred radiation has a wavelength around 530 nm. This method is effective for destroying both Gram-positive and Gram-negative bacteria, and is particularly effective in areas where complex media such as blood serum, blood or saliva are also present.
摘要翻译：公开了一种利用Safranin O结合电磁辐射来破坏体内微生物，特别是细菌的方法和组合物。在优选的方法中，将包含番红蛋白O的组合物引入治疗区域。在经过足够的时间后，将适当波长的辐射施加到该区域以激活番红蛋白O，并通过光动力学反应来破坏细菌。优选的辐射具有约530nm的波长。这种方法对于破坏革兰氏阳性和革兰氏阴性菌都是有效的，并且在存在复合培养基如血清，血液或唾液的地区特别有效。

5. 发明授权

US09409037B2 Enhanced anti-microbial PDT 有权
标题翻译：增强抗微生物PDT
公开(公告)号：US09409037B2
公开(公告)日：2016-08-09
申请号：US13006274
申请日：2011-01-13
申请人： Volker Albrecht , Gerhard Wieland , Burkhard Gitter , Wolfgang Neuberger
发明人： Volker Albrecht , Gerhard Wieland , Burkhard Gitter , Wolfgang Neuberger
IPC分类号： A61N5/06 , A61M1/36 , A61L2/00
CPC分类号： A61N5/062 , A61L2/0029 , A61L2/0052 , A61L2202/21 , A61M1/3681 , A61M1/3686 , A61N5/0624 , A61N2005/063 , A61N2005/0652
摘要： Methods and devices to eliminate, reduce, destroy and/or inhibit undesired body fluid species, such as pathogen microbes and deteriorated or malignant cells in complex environments like blood, serum and other body fluids are provided. In preferred embodiments, an antimicrobial photodynamic therapy (PDT) treatment is given that effectively inactivates, reduces and/or destroys both Gram (−) and Gram (+) bacteria in complex body fluids. Methods to enhance antimicrobial PDT activity include administering a photosensitizer to bacteria-contaminated fluid, after a dwell time guiding bacteria-contaminated fluid with photosensitizer through a channel, emitting radiation preferably in an intermittent manner, and restoring treated body fluids to corresponding body regions. Electromagnetic radiation is preferably delivered intermittently with pulse width based on treatment parameters. Additionally, the method/device diminishes adverse host's inflammatory responses by neutralizing the biological activity of pathogenic microorganism fragments and reducing and/or removing pathogenic microorganism fragments responsible for it.
摘要翻译：提供了用于消除，减少，破坏和/或抑制诸如病原体微生物和诸如血液，血清和其他体液的复杂环境中的恶化或恶性细胞的不期望的体液物质的方法和装置。在优选的实施方案中，给出了在复合体液中有效灭活，减少和/或破坏革兰氏（ - ）和革兰氏阴性（+）细菌的抗微生物光动力疗法（PDT）治疗。增强抗微生物PDT活性的方法包括在通过通道引导细菌污染的流体与光敏剂停留时间之后，向细菌污染的流体施用光敏剂，优选以间歇方式发射辐射，并将经处理的体液恢复到相应的身体区域。基于治疗参数，电磁辐射优选间歇地以脉冲宽度递送。此外，该方法/装置通过中和致病微生物片段的生物活性并减少和/或除去负责其的病原微生物片段来减少不良宿主的炎症反应。

6. 发明申请

US20110178580A1 ENHANCED ANTI-MICROBIAL PDT 有权
标题翻译：增强抗微生物PDT
公开(公告)号：US20110178580A1
公开(公告)日：2011-07-21
申请号：US13006274
申请日：2011-01-13
申请人： Volker Albrecht , Gerhard Wieland , Burkhard Gitter , Wolfgang Neuberger
发明人： Volker Albrecht , Gerhard Wieland , Burkhard Gitter , Wolfgang Neuberger
IPC分类号： A61N5/06
CPC分类号： A61N5/062 , A61L2/0029 , A61L2/0052 , A61L2202/21 , A61M1/3681 , A61M1/3686 , A61N5/0624 , A61N2005/063 , A61N2005/0652
摘要： Present invention provides enhanced methods and improved devices to eliminate, reduce, destroy and/or inhibit undesired body fluid species, such as pathogen microbes and deteriorated or malignant cells in complex environments like blood, serum and other body fluids. In preferred embodiments, present invention provides an antimicrobial PDT treatment that effectively inactivates, reduces and/or destroys both Gram (−) and Gram (+) bacteria in complex body fluids. Methods to enhance antimicrobial PDT activity includes the steps of administering a photosensitizer to bacteria-contaminated fluid, after a dwell time guiding bacteria-contaminated fluid with photosensitizer through a channel, emitting radiation preferably in an intermittent manner, and restoring treated body fluids to corresponding body regions. Electromagnetic radiation is preferably delivered intermittently with pulse width based on treatment parameters. Preferred device embodiments comprise guiding channels and at least one electromagnetic radiation source, arranged separately or in sequence. Preferably, laser device or LED-panels are used to deliver electromagnetic radiation to activate the photosensitizer. When used with preferred photosensitizer composition based on Safranin O, preferred laser radiation wavelength is in the range of 500-580 nm. Additionally, present invention diminishes adverse host's inflammatory responses by neutralizing the biological activity of pathogenic microorganism fragments and reducing and/or removing pathogenic microorganism fragments responsible for it.
摘要翻译：本发明提供增强的方法和改进的装置，以消除，减少，破坏和/或抑制不期望的体液物质，例如病原体微生物和复杂环境如血液，血清和其它体液中的恶化或恶性细胞。在优选的实施方案中，本发明提供了在复合体液中有效灭活，减少和/或破坏革兰氏（ - ）和革兰氏阴性（+）细菌的抗微生物PDT治疗。增强抗菌PDT活性的方法包括以下步骤：在细菌污染的流体与光敏剂通过通道引导细菌污染的流体停留时间之后，向细菌污染的流体施用光敏剂，优选以间歇的方式发射辐射，并将经处理的体液恢复到对应的身体地区。基于治疗参数，电磁辐射优选间歇地以脉冲宽度递送。优选的装置实施例包括分开或依次布置的引导通道和至少一个电磁辐射源。优选地，激光装置或LED面板用于递送电磁辐射以激活光敏剂。当与基于Safranin O的优选光敏剂组合物一起使用时，优选的激光辐射波长在500-580nm的范围内。此外，本发明通过中和病原微生物片段的生物活性来减少不良宿主的炎症反应，还原和/或除去负责其的病原微生物片段。

7. 发明申请

US20050059731A1 Erythrosin-based antimicrobial photodynamic therapy compound and its use 审中-公开
标题翻译：红霉素类抗微生物光动力治疗药物及其用途
公开(公告)号：US20050059731A1
公开(公告)日：2005-03-17
申请号：US10860297
申请日：2004-06-03
申请人： Volker Albrecht , Burkhard Gitter
发明人： Volker Albrecht , Burkhard Gitter
IPC分类号： A61K31/366 , A61N5/06 , A61N1/30
CPC分类号： A61K9/0063 , A61K31/366 , A61K41/0057 , A61N5/062
摘要： A method and composition for destroying microbes, especially bacteria, in the body utilizing Erythrosin B in conjunction with electromagnetic radiation is disclosed. In a preferred method, a composition comprising Erythrosin B is introduced to a treatment area. After a sufficient period of time has elapsed, radiation of a suitable wavelength is applied to the area to activate the Erythrosin B and by a photodynamic reaction to destroy the bacteria. Preferred radiation has a wavelength around 530 nm. Erythrosin B is incorporated within a gel, which acts to restrict the photodynamic action proximate to the biofilm, thus ensuring that only unwanted bacteria is effected and natural microflora is unharmed. This method is effective for destroying at least Gram-positive bacteria, and is particularly effective in areas where complex media such as saliva are also present.
摘要翻译：公开了一种利用红血球蛋白B结合电磁辐射来破坏体内微生物，特别是细菌的方法和组合物。在优选的方法中，将包含红血球蛋白B的组合物引入治疗区域。在经过足够的时间后，将适当波长的辐射施加到该区域以激活红霉素B，并通过光动力学反应来破坏细菌。优选的辐射具有约530nm的波长。红血球蛋白B掺入凝胶内，其作用是限制靠近生物膜的光动力学作用，从而确保只有不需要的细菌受到影响，并且天然的微生物群落没有受到伤害。该方法对于破坏至少革兰氏阳性菌是有效的，并且在还存在诸如唾液的复合介质的区域中是特别有效的。

8. 发明授权

US06416785B1 Molecular probes for targeting of cell density-indicating compounds 失效
标题翻译：用于靶向细胞密度指示化合物的分子探针
公开(公告)号：US06416785B1
公开(公告)日：2002-07-09
申请号：US09644952
申请日：2000-08-23
申请人： Dieter Riesenberg , Volker Schroeckh , Burkhard Gitter , Wolfgang Neuberger
发明人： Dieter Riesenberg , Volker Schroeckh , Burkhard Gitter , Wolfgang Neuberger
IPC分类号： A61K9127
CPC分类号： A61K31/00
摘要： A new approach for targeting chemotherapeutics to focal bacterial infections is provided. Such focal infections are characterized by high densities of different bacteria and thus high concentrations of their extracellular signal molecules sensing the cell density. In gram-negative bacteria, one of such signal molecules is acyl-homoserine lactone (acyl-HSL, member of the autoinducer family AI-1), wherein species-specificity is achieved by acyl-residues, and HSLs are common for all gram-negative bacteria. In gram-positive bacteria, oligopeptides secreted by the bacteria communicate the cell density. In addition, there are cell density signal molecules (members of the autoinducer family AI-2) which communicate between gram-positive and gram-negative bacteria. The general scheme of the present invention is molecular modules that comprise both a targeting component and a chemotherapeutical component which serves for photodynamic antimicrobial chemotherapy (PACT). One preferred embodiment of the present invention is to target photosensitizers to the extracellular signal molecules instead of on the bacteria themselves. Targeting of the photosensitizers is mediated via molecules with efficient binding to the HSL-moiety of the acyl-HSL, so that a broad spectrum of gram-negative bacteria can be knocked out. Photosensitizers used in the present invention can be packed into special liposomes with lipid chelators or multiple coupled to dendrimers, so that they are especially effective for PACT. In addition, selected molecules with high affinity to a common moiety of such signal molecules, like HSL, may be used as molecular probes for the search of yet undiscovered cell density dependent signals.
摘要翻译：提供了一种将化学治疗剂靶向局灶性细菌感染的新方法。这种局部感染的特征在于不同细菌的高密度，因此其细胞外信号分子的高浓度感测细胞密度。在革兰氏阴性细菌中，这种信号分子之一是酰基高丝氨酸内酯（酰基-HSL，自身诱导者家族AI-1的成员），其中通过酰基残基实现物种特异性，并且HSL对于所有革兰氏阴性细菌是常见的，阴性细菌。在革兰氏阳性细菌中，由细菌分泌的寡肽传播细胞密度。此外，存在细胞密度信号分子（自体诱导者家族成员AI-2），其在革兰氏阳性和革兰氏阴性细菌之间进行通信。本发明的一般方案是包含用于光动力学抗微生物化疗（PACT）的靶向组分和化学治疗组分的分子模块。本发明的一个优选实施方案是将光敏剂靶向细胞外信号分子而不是细菌本身。光敏剂的靶向通过与酰基HSL的HSL-部分有效结合的分子介导，从而可以敲除广谱的革兰氏阴性细菌。本发明中使用的光敏剂可以用脂质螯合剂或多个偶联至树状聚合物的特殊脂质体包装，使得它们对于PACT特别有效。此外，对这种信号分子（如HSL）的共同部分具有高亲和力的选择的分子可以用作搜索尚未发现的细胞密度相关信号的分子探针。

9. 发明授权

US09216166B2 Anti-microbial photodynamic therapy 有权
标题翻译：抗微生物光动力疗法
公开(公告)号：US09216166B2
公开(公告)日：2015-12-22
申请号：US12375241
申请日：2007-07-27
申请人： Nikolay E. Nifantiev , Burkhard Gitter , Dmitri V. Yashunsky
发明人： Nikolay E. Nifantiev , Burkhard Gitter , Dmitri V. Yashunsky
IPC分类号： A61K31/407 , A61K47/48 , A61K41/00
CPC分类号： A61K31/407 , A61K41/0071 , A61K47/64
摘要： Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The key to these conjugates is a special spacer connecting at least one photosensitizer to a microorganism receptor (vector) which in turn binds selectively to the surface of a microorganism bringing about photo-destruction upon irradiation. Spacers having hydrophilic structure such as ethylene glycol units and amino carboxyl end capped ethylene glycol units must be used for linking the vector to the photosensitizer. In a preferred embodiment a spacer would have at least 3 ethylene glycol units and be end capped with a carboxyl group on one end and a amino group at the other end. The present invention effectively works to combat bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or at least nearby. Spacers of selected length and structure, in preferred embodiments, are used for linking the vector to the photosensitizer. These conjugate are found to be very effective in combating bacterial infection in the real patient-related environments where blood, serum and other body fluids are always present or a least nearby. A method of use is also provided.
摘要翻译：提供了用于治疗和预防人和动物中致病微生物引起的感染性疾病的抗微生物分子缀合物。这些缀合物的关键是将至少一种光敏剂与微生物受体（载体）连接的特殊间隔物，微生物受体（载体）又依赖于微生物的表面结合，从而在照射时引起光损伤。必须使用具有亲水性结构的间隔物，例如乙二醇单元和氨基羧基封端的乙二醇单元，用于将载体与光敏剂连接。在优选的实施方案中，间隔物将具有至少3个乙二醇单元，并且在一端具有羧基并在另一端具有氨基末端封端。本发明有效地抵抗在血液，血清和其他体液总是存在或至少在附近的真实的患者相关环境中的细菌感染。在优选实施方案中，所选长度和结构的间隔物用于将载体连接至光敏剂。发现这些结合物在血液，血清和其他体液总是存在或至少在附近的真实患者相关环境中对抗细菌感染是非常有效的。还提供了一种使用方法。

10. 发明申请

US20120094269A1 Novel method for microbes depletion in human blood or full serum using antimicrobial photodynamic laser therapy 有权
标题翻译：使用抗微生物光动力激光治疗人类血液或全血清微生物消耗的新方法
公开(公告)号：US20120094269A1
公开(公告)日：2012-04-19
申请号：US13375799
申请日：2010-06-02
申请人： Gerhard D. Wieland , Albrecht Volker , Karl-Heinz Völpel , Burkhard Gitter
发明人： Gerhard D. Wieland , Albrecht Volker , Karl-Heinz Völpel , Burkhard Gitter
IPC分类号： A01N1/02 , C12M1/42
CPC分类号： A61L2/0076 , A61L2202/22 , A61M1/0272 , A61M1/3683 , A61M1/3686
摘要： Treatment methods/devices are provided for attenuating/inactivating the pathogenic microbes found in biological fluids e.g. blood/blood products including human single-donor-fresh-frozen-plasma, platelet concentrate, red blood cells, blood clotting factors. An Antimicrobial Photodynamic Therapy method is used to eliminate multiple (resistant) bacteria, viral agents, fungi, parasites and other undetected or non-easily detected pathogenic microbes or particles in blood and blood products without affecting their biological properties. Resistant bacteria are difficult to be eliminated. This is especially true in the case for S. aureus and related strains, Staphylococcus epidermidis or Propionibacterium acnes, Borrelia species and other bacteria found on skin. Further embodiments eliminate undetected or non-easily detected viral agents contaminating blood/blood products responsible for spreading hepatitis, Acquired ImmunoDeficiency Syndrome and other blood borne viral diseases. Human Immunodeficiency, hepatitis B and hepatitis C viruses have emerged as major blood borne infections. Numerous parasites transmitted through bloods and derived products are also eliminated by these processes/devices.
摘要翻译：提供治疗方法/装置用于减弱/灭活生物流体中发现的致病微生物，例如血液/血液制品包括人类单供体 - 新鲜冷冻血浆，血小板浓缩物，红细胞，凝血因子。抗菌光动力治疗方法用于消除血液和血液制品中的多种（抗性）细菌，病毒剂，真菌，寄生虫和其他未检出或非易感的致病微生物或颗粒，而不影响其生物学性质。抗性细菌难以消除。在金黄色葡萄球菌和相关菌株，表皮葡萄球菌或痤疮丙酸杆菌，疏螺旋体属和皮肤上发现的其他细菌的情况下尤其如此。进一步的实施方案消除污染负责传播肝炎的血液/血液制品的未检测到的或非易于检测的病毒剂，获得性免疫缺陷综合征和其他血液传播的病毒性疾病。人类免疫缺陷病毒，乙型肝炎和丙型肝炎病毒已经成为主要的血源性感染。这些过程/装置也消除了通过血液和衍生产物传播的许多寄生虫。

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